Recent interest in nanomedicine has skyrocketed because of mRNA vaccine lipid
nanoparticles (LNPs) against COVID-19. Ironically, despite this success, the innovative
nexus between nanotechnology and biochemistry, and the impact of nanoparticles on enzyme
biochemical activity is poorly understood. The studies of this group on zinc
nanoparticle (ZNP) compositions suggest that nanorod morphologies are preferred and that
ZNP doped with manganese or iron can increase activity against model enzymes such as
luciferase, DNA polymerase, and β-galactosidase (β-Gal), with the latter
previously being associated with antimicrobial activity. SARS-CoV-2 encodes several of
these types of oxido-reductase, polymerase, or hydrolase types of enzymes, and while
metamaterials or nanoparticle composites have become important in many fields, their
application against SARS-CoV-2 has only recently been considered. Recently, this group
discovered the antiviral activity of manganese-doped zinc sulfide (MnZnS), and here the
interactions of this nanoparticle composite with β-Gal, angiotensin converting
enzyme (ACE), and human ACE2 (hACE2), the SARS-CoV-2 receptor, are demonstrated. Low UV,
circular dichroism, and zeta potential results confirm their enzyme interaction and
inhibition by fluorometric area under the curve (AUC) measurements. The IC
50
of enzyme activity varied depending on the manganese percentage and surface ranging from
20 to 50 μg/mL. MnZnS NPs give a 1–2 log order inhibition of SARS-CoV-2;
however, surface-capping with cysteine does not improve activity. These data suggest
that Mn substituted ZNP interactions to hACE2 and potentially other enzymes may underlie
its antiviral activity, opening up a new area of pharmacology ready for preclinical
translation.